NEUROPHYSIOLOGY | Neuroendocrine Cells

Abstract

Pulmonary neuroendocrine (NE) cells are widely distributed within the airway epithelium of mammalian lungs. NE cells are either found as a solitary cell or as part of distinctive innervated cell clusters, neuroepithelial bodies (NEBs), both of which have abundant cytoplasmic dense core vesicles (DCVs), the storage site for amine (serotonin, 5-HT) and peptides (bombesin, gastrin-releasing peptide) that act as neurotransmitters, neuromodulators, and growth factors. During lung development NE cells/NEBs express a mixed epithelial, neural, and neuroendocrine phenotype and their differentiation is directed by proneural basic helix–loop–helix factors. In fetal lung, these cells appear numerous compared to the adult and are thought to be involved in lung morphogenesis, while postnatally NEBs function as hypoxia-sensitive airway chemoreceptors. Hypoxia activates a membrane-bound molecular complex composed of an oxygen-sensitive K+ channel coupled to a multicomponent NADPH oxidase leading to exocytosis of DCVs with release of 5-HT and other mediators acting locally or via vagal afferents transmitting the hypoxia signal to the brainstem. NEB cells also express multiple neurotransmitter receptors involved in the chemotransmission of hypoxia and other stimuli. The biological complexity and multifunctional nature of neuroendocrine cell systems implies wide-ranging involvement in normal lung functions and in the pathophysiology of a variety of pediatric as well as adult respiratory diseases including lung carcinogenesis.